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Publicações

Publicações por João Manuel Pedrosa

2021

Extracting neuronal activity signals from microscopy recordings of contractile tissue using B-spline Explicit Active Surfaces (BEAS) cell tracking

Autores
Kazwiny, Y; Pedrosa, J; Zhang, ZQ; Boesmans, W; D'hooge, J; Vanden Berghe, P;

Publicação
SCIENTIFIC REPORTS

Abstract
Ca2+ imaging is a widely used microscopy technique to simultaneously study cellular activity in multiple cells. The desired information consists of cell-specific time series of pixel intensity values, in which the fluorescence intensity represents cellular activity. For static scenes, cellular signal extraction is straightforward, however multiple analysis challenges are present in recordings of contractile tissues, like those of the enteric nervous system (ENS). This layer of critical neurons, embedded within the muscle layers of the gut wall, shows optical overlap between neighboring neurons, intensity changes due to cell activity, and constant movement. These challenges reduce the applicability of classical segmentation techniques and traditional stack alignment and regions-of-interest (ROIs) selection workflows. Therefore, a signal extraction method capable of dealing with moving cells and is insensitive to large intensity changes in consecutive frames is needed. Here we propose a b-spline active contour method to delineate and track neuronal cell bodies based on local and global energy terms. We develop both a single as well as a double-contour approach. The latter takes advantage of the appearance of GCaMP expressing cells, and tracks the nucleus' boundaries together with the cytoplasmic contour, providing a stable delineation of neighboring, overlapping cells despite movement and intensity changes. The tracked contours can also serve as landmarks to relocate additional and manually-selected ROIs. This improves the total yield of efficacious cell tracking and allows signal extraction from other cell compartments like neuronal processes. Compared to manual delineation and other segmentation methods, the proposed method can track cells during large tissue deformations and high-intensity changes such as during neuronal firing events, while preserving the shape of the extracted Ca2+ signal. The analysis package represents a significant improvement to available Ca2+ imaging analysis workflows for ENS recordings and other systems where movement challenges traditional Ca2+ signal extraction workflows.

2021

A multi-task CNN approach for lung nodule malignancy classification and characterization

Autores
Marques, S; Schiavo, F; Ferreira, CA; Pedrosa, J; Cunha, A; Campilho, A;

Publicação
EXPERT SYSTEMS WITH APPLICATIONS

Abstract
Lung cancer is the type of cancer with highest mortality worldwide. Low-dose computerized tomography is the main tool used for lung cancer screening in clinical practice, allowing the visualization of lung nodules and the assessment of their malignancy. However, this evaluation is a complex task and subject to inter-observer variability, which has fueled the need for computer-aided diagnosis systems for lung nodule malignancy classification. While promising results have been obtained with automatic methods, it is often not straightforward to determine which features a given model is basing its decisions on and this lack of explainability can be a significant stumbling block in guaranteeing the adoption of automatic systems in clinical scenarios. Though visual malignancy assessment has a subjective component, radiologists strongly base their decision on nodule features such as nodule spiculation and texture, and a malignancy classification model should thus follow the same rationale. As such, this study focuses on the characterization of lung nodules as a means for the classification of nodules in terms of malignancy. For this purpose, different model architectures for nodule characterization are proposed and compared, with the final goal of malignancy classification. It is shown that models that combine direct malignancy prediction with specific branches for nodule characterization have a better performance than the remaining models, achieving an Area Under the Curve of 0.783. The most relevant features for malignancy classification according to the model were lobulation, spiculation and texture, which is found to be in line with current clinical practice.

2021

Automated analysis of 3D-echocardiography using spatially registered patient-specific CMR meshes

Autores
Zhao, D; Ferdian, E; Maso Talou, G; Quill, G; Gilbert, K; Babarenda Gamage, T; Wang, V; Pedrosa, J; D"hooge, J; Legget, M; Ruygrok, P; Doughty, R; Camara, O; Young, A; Nash, M;

Publicação
European Heart Journal - Cardiovascular Imaging

Abstract
Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart Foundation (NHF) of New Zealand Health Research Council (HRC) of New Zealand Artificial intelligence shows considerable promise for automated analysis and interpretation of medical images, particularly in the domain of cardiovascular imaging. While application to cardiac magnetic resonance (CMR) has demonstrated excellent results, automated analysis of 3D echocardiography (3D-echo) remains challenging, due to the lower signal-to-noise ratio (SNR), signal dropout, and greater interobserver variability in manual annotations. As 3D-echo is becoming increasingly widespread, robust analysis methods will substantially benefit patient evaluation.  We sought to leverage the high SNR of CMR to provide training data for a convolutional neural network (CNN) capable of analysing 3D-echo. We imaged 73 participants (53 healthy volunteers, 20 patients with non-ischaemic cardiac disease) under both CMR and 3D-echo (<1 hour between scans). 3D models of the left ventricle (LV) were independently constructed from CMR and 3D-echo, and used to spatially align the image volumes using least squares fitting to a cardiac template. The resultant transformation was used to map the CMR mesh to the 3D-echo image. Alignment of mesh and image was verified through volume slicing and visual inspection (Fig. 1) for 120 paired datasets (including 47 rescans) each at end-diastole and end-systole. 100 datasets (80 for training, 20 for validation) were used to train a shallow CNN for mesh extraction from 3D-echo, optimised with a composite loss function consisting of normalised Euclidian distance (for 290 mesh points) and volume. Data augmentation was applied in the form of rotations and tilts (<15 degrees) about the long axis. The network was tested on the remaining 20 datasets (different participants) of varying image quality (Tab. I). For comparison, corresponding LV measurements from conventional manual analysis of 3D-echo and associated interobserver variability (for two observers) were also estimated. Initial results indicate that the use of embedded CMR meshes as training data for 3D-echo analysis is a promising alternative to manual analysis, with improved accuracy and precision compared with conventional methods. Further optimisations and a larger dataset are expected to improve network performance. (n?=?20) LV EDV (ml) LV ESV (ml) LV EF (%) LV mass (g) Ground truth CMR 150.5 ± 29.5 57.9 ± 12.7 61.5 ± 3.4 128.1 ± 29.8 Algorithm error -13.3 ± 15.7 -1.4 ± 7.6 -2.8 ± 5.5 0.1 ± 20.9 Manual error -30.1 ± 21.0 -15.1 ± 12.4 3.0 ± 5.0 Not available Interobserver error 19.1 ± 14.3 14.4 ± 7.6 -6.4 ± 4.8 Not available Tab. 1. LV mass and volume differences (means ± standard deviations) for 20 test cases. Algorithm: CNN – CMR (as ground truth). Abstract Figure. Fig 1. CMR mesh registered to 3D-echo.

2021

Can shear wave imaging distinguish between diffuse interstitial and replacement myocardial fibrosis?

Autores
Petrescu, A; Cvijic, M; Bezy, S; Santos, P; Duchenne, J; Orlowska, M; Pedrosa, J; Degtiarova, G; Van Keer, J; Von Bardeleben, S; Droogne, W; Van Cleemput, J; Bogaert, J; D"hooge, J; Voigt, J;

Publicação
European Heart Journal - Cardiovascular Imaging

Abstract
Abstract Funding Acknowledgements Type of funding sources: None. Background   Diffuse interstitial or myocardial replacement fibrosis are common features of a large variety of cardiomyopathies. These alterations contribute to functional changes, particularly to an increased myocardial stiffness (MS). Histological examination is the gold standard for myocardial fibrosis quantification, however, it requires endomyocardial biopsy which is invasive and not without risks. Cardiac magnetic resonance (CMR) can characterize the extent of both diffuse and replacement fibrosis and may have prognostic value in various cardiomyopathies. Echocardiographic shear wave (SW) elastography is an emerging approach for measuring MS in vivo. SWs occur after mechanical excitation of the myocardium, e.g. after mitral valve closure (MVC), and their propagation velocity is directly related to MS, thus providing an opportunity to assess stiffness at end-diastole. Purpose The aim was to investigate if velocities of natural SW can distinguish between interstitial and replacement fibrosis.  Methods We prospectively enrolled 47 patients (22 patients after heart transplant [54.2?±?15.8 years, 82.6% male] and 25 patients with established hypertrophic cardiomyopathy [54.0?±?13.5 years, 80.0% male]) undergoing CMR during their check-up. We performed SW elastography in parasternal long axis views of the LV using a fully programmable experimental scanner (HD-PULSE) equipped with a clinical phased array transducer (Samsung Medison P2-5AC) at 1100?±?250 frames per second. Tissue acceleration maps were extracted from an anatomical M-mode line along the midline of the LV septum. The SW propagation velocity at MVC was measured as the slope in the M-mode image. All patients underwent T1 mapping as well as late gadolinium enhancement (LGE) cardiac magnetic resonance at 1.5 T to assess the presence of diffuse or replacement fibrosis (Figure A). Therefore, patients were divided in three groups: no fibrosis, diffuse fibrosis and replacement fibrosis. Results Mechanical SW’s were observed in 46 subjects starting immediately after MVC and propagating from the LV base to the apex. SW propagation velocity at MVC correlated well with native myocardial T1 values (r?=?0.65, p?<?0.0001) and differed significantly among groups (p?<?0.0001), with a significant post-test between any pair of groups (Figure B). SW velocities below a cut-off of 6.01 m/s showed the highest accuracy to identify patients without any type of fibrosis (sensitivity 88 %, specificity 89%, area under the curve?=?0.93) (Figure C). A cut-off of 8.11 m/s could distinguish replacement fibrosis from diffuse fibrosis with a sensitivity and specificity of 59% and 92 %, respectively (area under the curve?=?0.80) (Figure D). Conclusions   Shear wave velocities after mitral valve closure can distinguish between normal and pathological myocardium and can detect differences between diffuse and replacement fibrosis. Abstract Figure.

2021

Interactive Segmentation via Deep Learning and B-Spline Explicit Active Surfaces

Autores
Williams, H; Pedrosa, J; Cattani, L; Housmans, S; Vercauteren, T; Deprest, J; D'hooge, J;

Publicação
MEDICAL IMAGE COMPUTING AND COMPUTER ASSISTED INTERVENTION - MICCAI 2021, PT I

Abstract
Automatic medical image segmentation via convolutional neural networks (CNNs) has shown promising results. However, they may not always be robust enough for clinical use. Sub-optimal segmentation would require clinician's to manually delineate the target object, causing frustration. To address this problem, a novel interactive CNN-based segmentation framework is proposed in this work. The aim is to represent the CNN segmentation contour as B-splines by utilising B-spline explicit active surfaces (BEAS). The interactive element of the framework allows the user to precisely edit the contour in real-time, and by utilising BEAS it ensures the final contour is smooth and anatomically plausible. This framework was applied to the task of 2D segmentation of the levator hiatus from 2D ultrasound (US) images, and compared to the current clinical tools used in pelvic floor disorder clinic (4DView, GE Healthcare; Zipf, Austria). Experimental results show that: 1) the proposed framework is more robust than current state-of-the-art CNNs; 2) the perceived workload calculated via the NASA-TLX index was reduced more than half for the proposed approach in comparison to current clinical tools; and 3) the proposed tool requires at least 13 s less user time than the clinical tools, which was significant (p = 0.001).

2021

Systematic Comparison of Left Ventricular Geometry Between 3D-Echocardiography and Cardiac Magnetic Resonance Imaging

Autores
Zhao, D; Quill, GM; Gilbert, K; Wang, VY; Houle, HC; Legget, ME; Ruygrok, PN; Doughty, RN; Pedrosa, J; D'hooge, J; Young, AA; Nash, MP;

Publicação
FRONTIERS IN CARDIOVASCULAR MEDICINE

Abstract
Aims: Left ventricular (LV) volumes estimated using three-dimensional echocardiography (3D-echo) have been reported to be smaller than those measured using cardiac magnetic resonance (CMR) imaging, but the underlying causes are not well-understood. We investigated differences in regional LV anatomy derived from these modalities and related subsequent findings to image characteristics.

Methods and Results: Seventy participants (18 patients and 52 healthy participants) were imaged with 3D-echo and CMR (<1 h apart). Three-dimensional left ventricular models were constructed at end-diastole (ED) and end-systole (ES) from both modalities using previously validated software, enabling the fusion of CMR with 3D-echo by rigid registration. Regional differences were evaluated as mean surface distances for each of the 17 American Heart Association segments, and by comparing contours superimposed on images from each modality. In comparison to CMR-derived models, 3D-echo models underestimated LV end-diastolic volume (EDV) by -16 +/- 22, -1 +/- 25, and -18 +/- 24 ml across three independent analysis methods. Average surface distance errors were largest in the basal-anterolateral segment (11-15 mm) and smallest in the mid-inferoseptal segment (6 mm). Larger errors were associated with signal dropout in anterior regions and the appearance of trabeculae at the lateral wall.

Conclusions: Fusion of CMR and 3D-echo provides insight into the causes of volume underestimation by 3D-echo. Systematic signal dropout and differences in appearances of trabeculae lead to discrepancies in the delineation of LV geometry at anterior and lateral regions. A better understanding of error sources across modalities may improve correlation of clinical indices between 3D-echo and CMR.

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